Novel mouse model for cholestasis‐induced liver fibrosis resolution by cholecystojejunostomy
Novel mouse model for cholestasis‐induced liver fibrosis resolution by cholecystojejunostomy
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通过胆囊空肠吻合术解决胆汁淤积引起的肝纤维化的新型小鼠模型
DOI：
10.1111/jgh.15406
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发表时间：
2021
影响因子：
4.1
通讯作者：
Uemoto Shinji
中科院分区：
文献类型：
--
作者：
Yoshino Kenji;Taura Kojiro;Iwaisako Keiko;Masano Yuki;Uemoto Yusuke;Kimura Yusuke;Nam Nguyen Hai;Nishino Hiroto;Ikeno Yoshinobu;Okuda Yukihiro;Nishio Takahiro;Yamamoto Gen;Seo Satoru;Uemoto Shinji
背景和目的在这个病因学根除的时代，对肝纤维化的研究变得越来越重要。相反，广泛的研究肝毒性损伤引起的肝纤维化的恢复，胆汁淤积性肝纤维化的回归已不充分检查，由于有限的可用性的动物models.MethodsWe研究了我们的新的再通小鼠模型的胆道梗阻，涉及胆囊和空肠（G-J吻合）之间的吻合内陷。转基因小鼠表达绿色荧光蛋白（GFP）下胶原1（α）1启动子进行G-J吻合术后14天胆管结扎（BDL），14天后处死。G-J吻合可显著逆转BDL诱导的肝纤维化。G-J吻合术后，BDL损伤小鼠肝脏中GFP和Thy-1免疫荧光双阳性的活化门静脉成纤维细胞（PF）变得不那么明显。吻合后肝脏中激活的PFs标志物的mRNA表达下调。BDL诱导基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）的表达。吻合后MMP-3、8和肝细胞生长因子表达进一步上调，而TIMP-1和TIMP-3表达明显下调。结论我们建立的G-J吻合模型与肝纤维化的消退有关，并通过胆道梗阻的再开放减少PF的激活，这将对研究胆汁淤积性肝纤维化的恢复过程有价值。
Background and AimStudies on the resolution of liver fibrosis are becoming more important in this era of etiologic eradication. In contrast to the extensive research on the recovery of liver fibrosis induced by hepatotoxic injuries, regression of cholestatic liver fibrosis has been insufficiently examined owing to the limited availability of animal models.MethodsWe examined our novel recanalization mice model of biliary obstruction, involving anastomosis between the gallbladder and jejunum (G–J anastomosis) by invagination. Transgenic mice expressing green fluorescent protein (GFP) under the collagen 1(α)1 promoter underwent G–J anastomosis 14 days after bile duct ligation (BDL) and were sacrificed 14 days later.ResultsTransaminase and total bilirubin levels decreased to almost normal values on day 14 after G–J anastomosis. G–J anastomosis resulted in dramatic reversal of liver fibrosis induced by BDL. Activated portal fibroblasts (PFs) double‐positive for GFP and Thy‐1 on immunofluorescence in the liver of BDL‐injured mice became less noticeable following G–J anastomosis. Messenger RNA expression of markers for activated PFs in the liver was downregulated after anastomosis. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) were induced by BDL. After anastomosis, expressions of MMP‐3, 8 as well as hepatocyte growth factor were further upregulated, whereas those of TIMP‐1 and TIMP‐3 were markedly downregulated.ConclusionsOur established G–J anastomosis model is associated with fibrosis resolution and reduced PF activation through reopening of bile duct obstruction and will be valuable for studying the recovery process of cholestatic liver fibrosis.
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胆道引流对胆道纤维化肝损伤修复的影响
影响因子：
2.2
作者：
R. Kemp;Whemberton Martins de Araújo;Adelson Antonio de Castro;J. Ardengh;L. Neder;J. D. dos Santos
通讯作者：
J. D. dos Santos
影响因子：
1.4
作者：
Huang X;Li CH;Zhang AQ;Kong Z;Gu WQ;Dong JH
通讯作者：
Dong JH
对已有肝硬化组织病理学证据的儿童进行胆汁减压
DOI：
10.1177/000313480206800917
发表时间：
2002
期刊：
The American Surgeon
影响因子：
--
作者：
C. Jackson;Yeming Wu;Shi Chenren;S. Sømme;W. Chwals;Donald C. Liu
通讯作者：
Donald C. Liu
胆汁性肝硬化的新概念
DOI：
--
发表时间：
1987
期刊：
Seminars in liver disease (Print)
影响因子：
--
作者：
J. Ludwig
通讯作者：
J. Ludwig
影响因子：
5.6
作者：
Latronico T;Mascia C;Pati I;Zuccala P;Mengoni F;Marocco R;Tieghi T;Belvisi V;Lichtner M;Vullo V;Mastroianni CM;Liuzzi GM
通讯作者：
Liuzzi GM